FDA Outlines Path Forward For Biosimilars

What Are Biosimilars?

Biosimilars are copycat versions of expensive biotechnology drugs. Although technically these "biosimilars" are not called generic.

Example of biologics made with recombinant DNA technology :
Erythropoietin = Epogen / stimulation of red blood cell production


In Todays News

FDA Outlines Path Forward For Biosimilars
Feb/11/2012 5:31 AM ET

(RTTNews) - Finally, the long overdue FDA guidance for approval of biosimilar products has been unveiled.

Though a legislation giving authority to the FDA to approve biosimilar products was enacted in March of 2010 itself, biosimilars manufacturers hav been waiting for a formal regulatory guidance on the approval pathway.

The long wait came to an end on February 9, 2012, with the FDA releasing 3 draft guidance documents on biosimilar product development.

Before a take a look at the draft guidance, here's what biological products and biosimilars mean, in simple terms.

Biological products, which are manufactured through biotechnology, are complex in structure and are derived from natural sources, or, in some cases, produced synthetically. Vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and proteins are examples of biological products. Being inherently very difficult to copy and replicate, biologics have not been subject to intense generic competition even after they lose patent protection.

A biosimilar, also known as follow-on biologic, or biopharmaceutical, is a biological product that is highly similar to a U.S.-licensed reference biological product. Biosimilars can only be proven to be "highly similar" and not "identical" to the reference product. And the reason - biologics being large and complex molecules, it is impossible for a manufacturer of biosimilars to exactly replicate the innovator's process. Therefore even subtle differences in the structure of follow-on biologics may lead to variations in safety or efficacy compared to the innovator biologics.

The FDA approval pathway for biosimilars is known as 351(k) and it was created under the Patient Protection and Affordable Care Act that was signed into law by President Obama on March 23, 2010. Through this new approval pathway, biological products are approved based on demonstrating they are biosimilar to, or interchangeable with, a biological product that is already approved by the FDA, which is called a reference product.

The three draft guidance documents issued by the FDA touch upon the scientific considerations in demonstrating biosimilarity to a reference product; quality considerations in demonstrating biosimilarity to a reference protein product, and answers to common questions from people interested in developing biosimilar products.

The FDA's guidance on scientific considerations in determining biosimilarity has three approaches namely,

* A stepwise approach of comparing the proposed product and the reference product with respect to structure, function, animal toxicity, human pharmacokinetics, pharmacodynamics , clinical immunogenicity, clinical safety and efficacy.
* The totality-of-the-evidence approach wherein the FDA will consider the totality of the data and information submitted in the application, including structural and functional characterization, nonclinical evaluation, human pharmacokinetics and pharmacodynamics data, clinical immunogenicity data, and clinical safety and effectiveness data.
* General considerations like no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.

The FDA's guidance on quality considerations in determining biosimilarity provides an overview of analytical factors to consider in demonstrating biosimilarity between a proposed protein product and the reference product.

The factors for consideration in assessing whether the products are highly similar are - genetic stability, manufacturing process, assessment of physicochemical properties of the proposed biosimilar product and the reference product, assessment of functional activity and receptor binding and immunochemical properties, to name a few.

The guidance, which provides answers to common questions from people interested in developing biosimilar products, seeks to promote transparency and gives a better picture regarding the appropriate statutory authority under which certain products will be regulated.

The FDA is accepting public comments on the three draft guidance documents.

Janet Woodcock, director of FDA's Center for Drug Evaluation and Research, said, "These draft documents are designed to help industry develop biosimilar versions of currently approved biological products, which can enhance competition and may lead to better patient access and lower cost to consumers."

Europe is currently the most advanced in terms of having established an approval pathway for biosimilars. The biosimilar pathway was established by the European Medicines Agency, or EMA, in 2006.

According to reports, nearly 14 biosimilars, including generic versions of human growth hormone, anemia treatment erythropoietin and G-CSF (Granulocyte colony-stimulating factor) that stimulates the production of white blood cells , have been approved by the European regulators under the biosimilar pathway.

The EMA follows the "similar biological medicinal products" approach, which means that in order to be considered a biosimilar, it needs to demonstrate similarity to a reference innovator biologic , in addition to comparable safety and efficacy. The EMA guidelines do not address the issue of interchangeability and it is for a physician to decide whether to treat a patient with the biosimilar or with the reference medicine. Since a biosimilar and its biological reference medicine are not identical they do not qualify to be automatically interchangeable as per approval standard in Europe.